Aniline → Tert-butyl 4-{1-[(acetylamino)methyl]-2-anilino-2-oxoethyl}benzoate

HRID 1919905Notes

Reaction equation

HRID 1919905 reaction equation
[C:1]([NH:4][CH2:5][CH:6]([C:10]1[CH:15]=[CH:14][C:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[CH:12][CH:11]=1)[C:7]([OH:9])=O)(=[O:3])[CH3:2].CCN=C=NCCCN(C)C.[CH:34]1[CH:35]=[CH:36][C:37]2N(O)N=[N:40][C:38]=2[CH:39]=1.NC1C=CC=CC=1>CN(C=O)C>[C:1]([NH:4][CH2:5][CH:6]([C:10]1[CH:15]=[CH:14][C:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[CH:12][CH:11]=1)[C:7]([NH:40][C:38]1[CH:39]=[CH:34][CH:35]=[CH:36][CH:37]=1)=[O:9])(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 6115AnilineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 576119543-(Acetylamino)-2-[4-(tert-butoxycarbonyl)phenyl]propanoic acid

Product 1

HCID 57611876Tert-butyl 4-{1-[(acetylamino)methyl]-2-anilino-2-oxoethyl}benzoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-(Acetylamino)-2-[4-(tert-butoxycarbonyl)phenyl]propanoic acid (222 mg, 0.72 mmol), EDCI (207 mg, 1.08 mmol), and HOBT (127 mg, 0.94 mmol) were dissolved in DMF (7 mL) and stirred for 5 minutes before adding aniline (99 μL, 1.08 mmol). After stirring at room temperature for 18 h, the solution was concentrated. The resulting residue was taken up in EtOAc, washed (water, sat. NaHCO3, brine), dried (MgSO4), and concentrated. Flash chromatography on silica (0-4% MeOH/DCM) afforded tert-butyl 4-{1-[(acetylamino)methyl]-2-anilino-2-oxoethyl}benzoate as an off-white solid. 1H NMR (DMSO-d6) δ10.18 (s, 1H), 8.08 (t, J=5.9 Hz, 1H), 7.84 (d, J=8.5 Hz, 2H), 7.56 (d, J=7.6 Hz, 2H), 7.46 (d, j=8.2 Hz, 2H), 7.25 (t, J=7.9 Hz, 2H), 7.00 (t, J=7.5 Hz, 1H), 4.03 (dd, J=8.2, 6.3 Hz, 1H), 3.51 (ddd, J=13.2, 8.4, 5.0 Hz, 1H), 3.42 (dt, J=12.9, 6.5 Hz, 1H), 1.74 (s, 3H), 1.50 (s, 9H). MS (ESI) calcd [M+H]+ 383.2, found 383.1.

Workup

  1. stirringAfter stirring at room temperature for 18 h
  2. concentrationthe solution was concentrated
  3. washwashed (water, sat. NaHCO3, brine)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-8028ca5bb3474fec9e002576e77d7e17
Source dataset
uspto-grants-2012_05
Patent number
US08168658B2

Reaction notes

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